rs3176183
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002693.3(POLG):c.1712+74del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000258 in 1,549,256 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 23)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
POLG
NM_002693.3 intron
NM_002693.3 intron
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.262
Genes affected
POLG (HGNC:9179): (DNA polymerase gamma, catalytic subunit) Mitochondrial DNA polymerase is heterotrimeric, consisting of a homodimer of accessory subunits plus a catalytic subunit. The protein encoded by this gene is the catalytic subunit of mitochondrial DNA polymerase. The encoded protein contains a polyglutamine tract near its N-terminus that may be polymorphic. Defects in this gene are a cause of progressive external ophthalmoplegia with mitochondrial DNA deletions 1 (PEOA1), sensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO), Alpers-Huttenlocher syndrome (AHS), and mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE). Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLG | NM_002693.3 | c.1712+74del | intron_variant | ENST00000268124.11 | |||
POLGARF | NM_001406557.1 | c.*984+74del | intron_variant | ||||
POLG | NM_001126131.2 | c.1712+74del | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLG | ENST00000268124.11 | c.1712+74del | intron_variant | 1 | NM_002693.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152016Hom.: 0 Cov.: 23
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GnomAD4 exome AF: 0.00000215 AC: 3AN: 1397240Hom.: 0 AF XY: 0.00000288 AC XY: 2AN XY: 695576
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 152016Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 74250
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ClinVar
Not reported inComputational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at